The long-term goal is to prevent the deleterious skeletal secondary complications that follow complete spinal cord injury (SCI). As many as twenty thousand Americans sustain an SCI each year, making it a public health concern of primary importance. Secondary complications from osteoporosis leads to bone fractures and renal complications that cost society between 4 and 7 billion dollars annually. A method to prevent bone loss after SCI would not only provide substantial savings, but could also profoundly improve the quality of life of people with SCI and keep them as viable candidates for the future cure. Recently, we verified that a certain dose of muscle stress preserved bone in the lower leg for 3 years following SCI. Unfortunately, many individuals with SCI cannot activate their muscles due to lower motor neuron injuries, too severe osteoporosis from chronic paralysis, or stimulation induced autonomic dysreflexia. Accordingly, we propose to use a novel approach to apply mechanical compressive stress and oscillatory (vibratory) stress both individually and in combination to determine if bone can be recovered in those with chronic paralysis and prevented in those with acute paralysis. Three specific aims will test these hypotheses using a servo-controlled vibration table and a pneumatically controlled compressive load. Each intervention will be unilateral so the opposite leg serves as a control. Aim 1 will determine the effects of a prescribed dose of mechanical load on bone density of the tibia over 1 year following SCI. Aim 2 will determine the effects of low load vibratory mechanical stress (30 Hz, 0.6 g,) on bone density of the tibia over 1 year following SCI. Aim 3 will determine the effects of both compressive load and vibratory input on bone density over the first year following SCI. A novel component of this study is it decomposes the stresses that may be present during resisted muscle contractions. We hypothesize the combined vibration and compressive load condition will induce the greatest osteoblast activity leading to over 20% more bone density in the trained limb. The mechanical compressive load and the vibratory stress will each have a lesser effect on bone density when compared to the combined condition. This research has the potential to rapidly translate to the clinical milieu to influence health quality after SCI. The proposed method not only has excellent potential for efficacy, but is also likely to be economical and easily integrated into the daily lives of people with SCI PUBLIC HEALTH RELEVANCE: This study examines the effects of high mechanically induced compressive loads and low vibratory loads on bone density in humans with spinal cord injury (SCI). Our recent findings with electrically induced muscle contractions raised the possibility that muscle stress that prevents bone loss is composed of both an oscillation (vibration) and a compressive force envelope. In this project, we decompose the stress signal and develop a method to apply both vibration and compression in humans with SCI, many of whom cannot use electrical stimulation.